52. Shenhab Zaig

Mechanisms underlying opioid-induced respiratory depression and analgesia in larval zebrafish.

6 Comments

  • Richard Horner says:

    Hi Shenhab. Nice poster and enjoyed the paper. Congrats

  • Tereza Martinu says:

    Hi Shenhab, this is nice. What are the differences between AB and TU strains of zebrafish? Are there known genetic differences? Which strain did you use for your subsequent experiments?

    • Shenhab says:

      Hi Dr. Martinu, thanks for your question! There are documented differences in behaviour (including in response to drugs of abuse) and baseline mRNA expression. Specifically, the two strains have been shown to be clearly segregated, likely due to heavy inbreeding in the AB strain.

      Given that the ABs were sensitive to opioids, we continued using them for experiments..

      Currently I’m using qPCR to look at differences in opioid receptor mRNA expression between the two strains.

  • Yara Zayed says:

    Great work Shenhab! Why do you think respiratory stimulants didn’t fully rescue opioid induced rep depression? Why did you choose N and L type calcium channels in relation to resp depression? And have you tried other targets? If not, are there any other targets that you think can be targeted?

    • Shenhab says:

      Thank you for your question, Dr. Zayed! The respiratory stimulants act on adjacent neurotransmitter systems and therefore “mask” the opioid respiratory depression rather than directly counteract it (i.e. with naloxone that actually outcompetes fentanyl at opioid receptor binding sites). Therefore, the stimulation is often not potent enough to totally reverse respiratory depression by opioids.

      Calcium channels are known to be a downstream mechanism of opioid receptor activation but the N- and L- types have not been investigated in the context of respiratory depression. Therefore, we wanted to target them as a novel mechanism.

      There are many known targets involved in the mechanisms of opioid inhibition like GIRK channels and b-arrestin that we can investigate moving forward!

Leave a Reply

Your email address will not be published. Required fields are marked *